A Hybrid Mechanism of Action for BCL6 in B Cells Defined by Formation of Functionally Distinct Complexes at Enhancers and Promoters

• DOI: 10.1016/j.celrep.2013.06.016
• Publication Date: 2013-08-01T20:03:13Z
• Authors: Katerina Hatzi; Yanwen Jiang; Chuanxin Huang; Francine Garrett-...; Micah D. Gearhart; Eugenia G. Gianno...; Paul Zumbo; Kevin Kirouac; Srividya Bhaskara; Jose M. Polo; Matthias Kormaksson; Alexander D. MacK...; Fengtian Xue; Christopher E. Mason; Scott W. Hiebert; Gilbert G. Prive; Leandro Cerchietti; Vivian J. Bardwell; Olivier Elemento; Ari Melnick
• Keywords: Corepressor; BCL6; Death-associated protein 6

The BCL6 transcriptional repressor is required for the development of germinal center (GC) B cells and diffuse large cell lymphomas (DLBCLs). Although can recruit multiple corepressors, its repression mechanism action in normal malignant unknown. We find that cells, mostly functions through two independent mechanisms are collectively essential to GC formation DLBCL, both mediated N-terminal BTB domain. These (1) a unique ternary BCOR-SMRT complex at promoters, with each corepressor binding symmetrical sites on homodimers linked specific epigenetic chromatin features, (2) "toggling" active enhancers poised but not erased conformation SMRT-dependent H3K27 deacetylation, which by HDAC3 opposed p300 histone acetyltransferase. Dynamic toggling provides basis undergo rapid phenotypic changes response signaling or environmental cues.